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1.
Environ Monit Assess ; 195(6): 766, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37249740

ABSTRACT

Heavy metals are well-recognised as environmental hazards due to their toxicity, environmental persistence, and bioaccumulation in living organisms. Human health is a crucial concern related to terrestrial and aquatic ecosystems poisoned by harmful heavy metals. Most heavy metals pollute the air, water, and soil, which can be fatal to humans. Humans and other species can be exposed to heavy metals through the food chain if the metals oxidise or combine with other environmental elements (such as water, soil, or air). Their entry into the food chain assures interactions with biological macromolecules in living systems, including humans, resulting in undesirable outcomes. Human poisonings have typically been caused by mercury, lead, chromium, cadmium, and arsenic. The build-up of these metals in living organisms causes various harmful consequences on different organs and tissues. The gravitas of heavy metal toxicity regarding molecular impact and carcinogenesis needs in-depth understanding despite the plethora of available data. Hence, additionally, we attempt to elaborate on the multi-level impact of five heavy metals and emphasise their role in cancer development. The rationale of this essay is thus to understand the role of five heavy metals, viz., lead (Pb), cadmium (Cd), chromium (Cr), arsenic (As), and mercury (Hg), in carcinogenesis. Heavy metals interfere with various biological functions, including proliferation, differentiation, repair of damage, and apoptosis. By comparing their modes of action, we see that these metals share common mechanisms for inducing toxicity, such as reactive oxygen species (ROS) production, antioxidant defence weakening, enzyme inactivation, and oxidative stress.


Subject(s)
Arsenic , Mercury , Metals, Heavy , Neoplasms , Humans , Cadmium/toxicity , Cadmium/analysis , Arsenic/toxicity , Arsenic/analysis , Ecosystem , Environmental Monitoring , Metals, Heavy/toxicity , Metals, Heavy/analysis , Mercury/analysis , Chromium/analysis , Soil , Neoplasms/chemically induced , Water , Carcinogenesis
2.
Acta Cytol ; 67(4): 333-345, 2023.
Article in English | MEDLINE | ID: mdl-36580900

ABSTRACT

INTRODUCTION: Pulmonary spindle cell and mesenchymal lesions are paradox for pathologists due to their rarity, overlapping morphology, and differentials ranging from benign to malignant lesions, and correct diagnosis is essential due to major treatment implications. This study highlights the role of fine-needle aspiration cytology, clot core biopsy, and immunohistochemistry in diagnosis of spindle cell lesions in lung, thus playing a key role in patient management. METHODS: It is a retrospective study of lung FNA with predominantly spindle and mesenchymal cells from 2015-2020 which were classified cytomorphologically into spindle, epithelioid, small round cell, and biphasic, and IHC panels are applied accordingly. FNA from mediastinum and chest wall was excluded. RESULTS: 60 cases of lung FNA with spindle and mesenchymal cells were identified and included 6 benign and 54 malignancies which included 24 primary pulmonary malignancies and 30 metastases. Most common primary malignancy was sarcomatoid carcinoma, and most common metastasis was malignant peripheral nerve sheath tumour. FNA was paucicellular in 7 cases and was reported as benign in 7 cases and malignant in 46 cases. There were two false-negative cases. One case of pulmonary blastoma was reported as inflammatory pseudotumour on cytology, and other case of chondrosarcoma was reported as chondroid tumour. Sensitivity and specificity of FNA in distinguishing benign lesions and malignancies were 93.8% and 100%, respectively. CONCLUSION: FNA along with clot core biopsy/cell block and IHC plays a pivotal role in the subsequent pathway taken for diagnostic or therapeutic management of these patients without the need for second sampling or trucut biopsies in a low resource setting.


Subject(s)
Carcinoma , Neoplasms, Connective and Soft Tissue , Humans , Biopsy, Fine-Needle , Retrospective Studies , Biopsy, Large-Core Needle , Carcinoma/pathology , Sensitivity and Specificity , Lung/pathology
3.
J Hum Reprod Sci ; 16(4): 324-332, 2023.
Article in English | MEDLINE | ID: mdl-38322644

ABSTRACT

Background: Amongst various other factors, oxygen (O2) concentration in embryo culture plays an important role in determining pregnancy outcomes in women undergoing in vitro fertilisation. Some studies have reported that lowering O2 levels in embryo culture provides better results. Aims: To explore the effects of low- and ultra-low- O2 concentrations (5% and 2%, respectively) in extended embryo culture on various outcome parameters of pregnancy. Settings and Design: This was a retrospective cross-sectional study. Materials and Methods: In this study 382 participants had their embryos cultured in varying O2 concentrations (5% or 2%), followed by either a fresh embryo transfer (ET) or frozen embryo transfer (FET). Outcomes such as pregnancy rate, implantation rate, abortion rate, twinning rate, and live birth rate were compared between the groups. Statistical Analysis Used: Chi square test was applied to compare the primary and secondary outcomes between different groups. Results: No significant differences were observed in pregnancy rate and implantation rate between 5% and 2% O2 groups, irrespective of their mode of ET. The abortion rate was significantly higher in 5% O2 group than in 2% group during FET (24.71% vs. 11.49%, P = 0.02). While the proportion of good-quality embryos was higher in 5% O2 group, these did not translate to better pregnancy outcomes. Additionally, embryos cultured in 2% O2 concentration had a significantly better implantation rate when they were transferred fresh rather than frozen (71.34% vs. 61.46%, P = 0.04). There were no other differences observed. Conclusion: Only marginal benefits were observed in switching human embryos to ultra-low O2 concentration after the initial days of culture.

4.
Mol Biol Rep ; 49(11): 10293-10305, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36097110

ABSTRACT

BACKGROUND: In cancer research, one of the most significant findings was to characterize the DNA repair deficiency as carcinogenic. Amongst the various repair mechanisms, mismatch repair (MMR) and direct reversal of DNA damage systems are designated as multilevel safeguards in the human genome. Defects in these elevate the rate of mutations and results in dire consequences like cancer. Of the several molecular signatures in human genome, tandem repeats (TRs) appear at various frequencies in the exonic, intronic, and regulatory regions of the DNA. Hypervariability among these repeats in the coding and non-coding regions of the genes is well characterized for solid tumours, but its significance in haematologic malignancies remains to be explored. The purpose of our study was to elucidate the role of nucleotide repeat instability in the coding and non-coding regions of 10 different repair genes in myeloid and lymphoid cell lines compared to the control samples. METHODS AND RESULTS: We selected MMR deficient extensively studied microsatellite instable colorectal cancer (HCT116), and MMR proficient breast cancer (MCF-7) cells along with underemphasized haematologic cancer cell lines to decipher the hypermutability of tandem repeats. A statistically significant TR variation was observed for MSH2 and MSH6 genes in 4 and 3 of the 6 cell lines respectively. KG1 (AML) and Daudi (Burkitt's lymphoma) were found to have compromised DNA repair competency with highly unstable nucleotide repeats. CONCLUSION: Taken together, the results suggest that mutable TRs in intronic and non-intronic regions of repair genes in blood cancer might have a tumorigenic role. Since this is a pilot study on cell lines, high throughput research in large cohorts can be undertaken to reveal novel diagnostic markers for unexplained blood cancer patients with normal karyotypes or otherwise with karyotypic defects.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Hematologic Neoplasms , Humans , Pilot Projects , Microsatellite Repeats/genetics , DNA Repair/genetics , Hematologic Neoplasms/genetics , Colonic Neoplasms/genetics , Cytogenetic Analysis , Nucleotides , DNA Mismatch Repair/genetics , Colorectal Neoplasms/metabolism , MutS Homolog 2 Protein/genetics , MutS Homolog 2 Protein/metabolism
5.
J Hum Reprod Sci ; 15(2): 138-142, 2022.
Article in English | MEDLINE | ID: mdl-35928462

ABSTRACT

Background: It is well established that high-quality semen can lead to an improved fertilisation rate. Ejaculatory abstinence (EA) certainly can influence sperm quality such as volume, count, motility and morphology. However, very few studies have addressed the influence of EA on intracytoplasmic sperm injection (ICSI) outcome and especially in males with severe oligo-asthenoteratozoospermia (OAT) syndrome. Aim: This study was undertaken with the purpose of evaluating the advantage of shorter abstinence period (1-h sequential ejaculation) in males with severe OAT syndrome on total usable embryo rate and thereby emphasising the potential application of consecutive ejaculate. Study Setting and Design: This retrospective cohort study consisted of all the infertile couples undergoing ICSI cycle with the indicated seminal characteristics who had consulted the tertiary care hospital between January 2021 and July 2021. Materials & Methods: All couples in the study had idiopathic male infertility. Retrospectively, two groups were analysed, i.e., Group A with 56 subjects in which first semen sample was used for ICSI cycle and another Group B with 41 subjects in which second semen sample collected within a shorter abstinence period of 1 h was used. Statistical Analysis: The data were descriptively analysed using GraphPad Prism (vs. 9.2). Unpaired t-test and analysis of variance test were used to determine the significance. P < 0.05 was considered statistically significant. Results: The age of female subjects in Group A was 29.9 ± 3.5 years while it was 29.4 ± 3.4 years in Group B. Similarly, the age of male subjects was 32.2 ± 3.6 years and 31.9 ± 4.1 years in Group A and Group B, respectively, with no statistical differences in any gender between the groups (P > 0.05). Apart from initial progressive motility (P = 0.004), none of the parameters such as total volume, total sperm count and morphology were significantly different (P > 0.05) between Group A and samples of Group B. Similarly, parameters such as volume (P = 0.006) and post-wash motility (P < 0.001) were significantly different between Group A and samples of Group B. However, there was no significant difference in sperm count and morphology (P > 0.05). Grade 1 embryos on day 3 were 345 (62.8%) in Group A and 170 (54.3%) in Group B. Overall, the total usable embryos in Group A and Group B were 222 (40.4%) and 148 (47.3%), respectively (P > 0.05). Conclusion: With regard to compromised sperm parameters, our findings do suggest that the second ejaculate is quite relevant to 'in vitro' reproductive treatments and a simple request for a second consecutive ejaculate (shorter abstinence period of 1 h) could provide the same results in terms of fertilisation. We observed the increased chances of usable embryos in the second ejaculate group.

6.
Mol Biol Rep ; 49(10): 9651-9671, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35397763

ABSTRACT

Melanoma is one of the most aggressive forms of skin cancer with a steady increase in global incidence and mortality rate over the past five decades. Paradoxically, both reduced and excessive sun exposure has been linked to increased risk of melanoma incidence and death. Although the histological classification of melanoma is useful in diagnosis, its molecular subtypes are often determined by somatic mutations, which could be UV-dependent or -independent. Multiple genes involved in cancer development are often mutated dysregulating molecular pathways with concomitant phenotypic heterogeneity. Hence, treating melanoma has been a challenge, with patients experiencing poor clinical outcomes to current therapeutic options. This presents an unmet need to understand the interaction of molecular networks underpinning melanogenesis. This review describes the crosstalk of signaling cascades in melanoma development and the putative druggable targets, with the view of elucidating newer and better therapeutic strategies for the disease.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/genetics , Melanoma/metabolism , Melanoma/therapy , Signal Transduction , Skin Neoplasms/genetics
7.
J Biomed Res ; 36(2): 77-97, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35260531

ABSTRACT

Melanoma is a relentless type of skin cancer which involves myriad signaling pathways which regulate many cellular processes. This makes melanoma difficult to treat, especially when identified late. At present, therapeutics include chemotherapy, surgical resection, biochemotherapy, immunotherapy, photodynamic and targeted approaches. These interventions are usually administered as either a single-drug or in combination, based on tumor location, stage, and patients' overall health condition. However, treatment efficacy generally decreases as patients develop treatment resistance. Genetic profiling of melanocytes and the discovery of novel molecular factors involved in the pathogenesis of melanoma have helped to identify new therapeutic targets. In this literature review, we examine several newly approved therapies, and briefly describe several therapies being assessed for melanoma. The goal is to provide a comprehensive overview of recent developments and to consider future directions in the field of melanoma.

8.
J Biomed Res ; 36(1): 1-9, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34963676

ABSTRACT

Development is a sophisticated process maintained by various signal transduction pathways, including the Hedgehog (Hh) pathway. Several important functions are executed by the Hh signaling cascade such as organogenesis, tissue regeneration, and tissue homeostasis, among various others. Considering the multiple functions carried out by this pathway, any mutation causing aberrant Hh signaling may lead to myriad developmental abnormalities besides cancers. In the present review article, we explored a wide range of diseases caused by aberrant Hh signaling, including developmental defects and cancers. Finally, we concluded this mini-review with various treatment strategies for Hh-induced diseases.

9.
Sci Rep ; 11(1): 10110, 2021 05 12.
Article in English | MEDLINE | ID: mdl-33980898

ABSTRACT

Plant derived products have steadily gained momentum in treatment of cancer over the past decades. Curcuma and its derivatives, in particular, have diverse medicinal properties including anticancer potential with proven safety as supported by numerous in vivo and in vitro studies. A defective Mis-Match Repair (MMR) is implicated in solid tumors but its role in haematologic malignancies is not keenly studied and the current literature suggests that it is limited. Nonetheless, there are multiple pathways interjecting the mismatch repair proteins in haematologic cancers that may have a direct or indirect implication in progression of the disease. Here, through computational analysis, we target proteins that are involved in rewiring of multiple signaling cascades via altered expression in cancer using various curcuma derivatives (Curcuma longa L. and Curcuma caesia Roxb.) which in turn, profoundly controls MMR protein function. These biomolecules were screened to identify their efficacy on selected targets (in blood-related cancers); aberrations of which adversely impacted mismatch repair machinery. The study revealed that of the 536 compounds screened, six of them may have the potential to regulate the expression of identified targets and thus revive the MMR function preventing genomic instability. These results reveal that there may be potential plant derived biomolecules that may have anticancer properties against the tumors driven by deregulated MMR-pathways.


Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Curcuma/chemistry , DNA Mismatch Repair/drug effects , Neoplasms/genetics , Plant Extracts/chemistry , Plant Extracts/pharmacology , Computational Biology , Gene Expression Regulation, Neoplastic/drug effects , Humans , Molecular Structure , Neoplasms/drug therapy , Neoplasms/metabolism , Rhizome/chemistry
10.
Diagn Cytopathol ; 49(8): 948-958, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33973738

ABSTRACT

BACKGROUND: Serous effusions (SE) in leukemic patients can be due to infections, therapy, volume overload, lymphatic obstruction or malignancy having implications on treatment and mortality. The objective of the present study is to highlight the spectrum of cytomorphology, immunophenotype, and cytogenetics in leukemic serous effusions (LSE). MATERIALS: Present study is retrospective and descriptive. We reviewed all the SE, which were reported as suspicious or positive of leukemic infiltration from 2016 to 2019 for cytomorphological features. CSF and effusions involved by lymphomas were excluded. Cyto-diagnosis was compared with primary proven diagnosis (by ancillary techniques) and disconcordant cases were analyzed. RESULTS: Out of total 9723 effusions, only 0.4% (n = 40) showed leukemic involvement and included nine cases of AML, three of B-ALL, 13 T-ALL, 2 MPAL, 6 CML, 5CLL, one each of chronic myelomonocytic leukemia and AML with myelodysplasia. The most common site of involvement was the pleural cavity (n = 30), followed by the peritoneal cavity (n = 7) and the pericardial cavity (n = 3). T -ALL (41.9%) was the most common leukemia involving pleural fluid followed by AML (23.3%). CML (42.8%) was the most common leukemia involving the ascitic fluid followed by B-ALL (28.6%). Accurate diagnosis was given on cytomorphology in 72.5% (29/40) cases and 15.0% (6/40) were reported as non-Hodgkin lymphoma. CONCLUSION: Cytology is an effective tool available to make a diagnosis of LSE. Nuclear indentations in large atypical cells and cells with eosinophilic granular cytoplasm with sparse or abundant eosinophils in the background are an important clue in favor of leukemia over lymphoma.


Subject(s)
Cytogenetic Analysis , Exudates and Transudates , Immunophenotyping , Leukemia , Lymphoma , Adolescent , Adult , Aged , Aged, 80 and over , Ascitic Fluid/immunology , Ascitic Fluid/pathology , Child , Child, Preschool , Cytodiagnosis/methods , Cytological Techniques/methods , Diagnosis, Differential , Exudates and Transudates/cytology , Exudates and Transudates/immunology , Female , Flow Cytometry/methods , Humans , Infant , Leukemia/diagnosis , Leukemia/pathology , Lymphoma/diagnosis , Lymphoma/pathology , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Pericardial Effusion/genetics , Pericardial Effusion/immunology , Pericardial Effusion/pathology , Pleural Effusion/genetics , Pleural Effusion/immunology , Pleural Effusion/pathology , Retrospective Studies
11.
Acta Cytol ; 65(2): 175-185, 2021.
Article in English | MEDLINE | ID: mdl-33316798

ABSTRACT

INTRODUCTION: Cytology provides crucial window for early diagnosis of malignant mesothelioma (MM) since it is often the first and easily available material for evaluation, resulting in early treatment. Still, its role is overlooked in the current treatment guidelines. The aim of this study is to determine the sensitivity of cytomorphology and role of subsequent ancillary techniques in diagnosing MM. METHODS: This is a 5-year retrospective analysis of MM in the tertiary oncology center to determine sensitivity of cytomorphology and subsequent role of immunohistochemistry (IHC) in final diagnosis of MM according to the guidelines for cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma (GCDMM) laid by International Mesothelioma Interest Group. Cytomorphology and immunocytochemistry from effusions and fine needle aspirations were analyzed. RESULTS: Sixty-two of 128 cases of MM had cytology and cytomorphological criteria described in GCDMM were fulfilled in 61.3% cases. Architectural atypia was useful in identifying cases with low cytological atypia. Overall sensitivity of cytomorphology was 73.01%. Sensitivity of effusion cytology was 77.8%. Subsequent IHC on cell blocks revealed the sensitivity as 100% for mesothelin, calretinin, and cytokeratin 5/6; 87.5% for thrombomodulin; and 50% for WT1, while CEA and TTF1 showed 100% specificity. Treatment was given based on final diagnosis of MM given after IHC on cytology material in only 25.8% cases. However, it was possible in additional 35.5% cases. Mean survival was 10 months when diagnosed by cytology, compared to 7 months by histology. CONCLUSIONS: Rather than ignoring the role of cytology in the diagnosis and treatment guidelines for MM, it is important to understand its strengths and limitations. Standardized guidelines in future can play an important role in more streamlined communication between cytopathologist and clinician.


Subject(s)
Early Detection of Cancer/standards , Mesothelioma, Malignant/pathology , Practice Guidelines as Topic/standards , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Biopsy/standards , Databases, Factual , Female , Humans , Immunohistochemistry/standards , India , Male , Mesothelioma, Malignant/chemistry , Mesothelioma, Malignant/mortality , Mesothelioma, Malignant/therapy , Middle Aged , Predictive Value of Tests , Prognosis , Reproducibility of Results , Retrospective Studies , Young Adult
12.
Diagn Cytopathol ; 49(1): 127-131, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32910561

ABSTRACT

OBJECTIVE: To determine the role of routine cervical Pap smears in detecting endometrial carcinomas. METHOD: A retrospective study was carried out from the histopathology archives for cases diagnosed as endometrial carcinomas with Pap smears within 6 months before histological diagnosis. The demographic details, reports of Pap smears and other tumor parameters on histopathology were noted. RESULTS: We identified 380 of 482 cases of endometrial carcinoma with a documented Pap smear within 6 months before histopathogical diagnosis. Out of 380 cases, 187 cases (49.2%) had shown abnormalities on Pap smear of which 80 cases (42%) were diagnosed as atypical glandular cells and 78 cases (41.7%) were diagnosed as adenocarcinoma. The presence of glandular abnormality on Pap smear significantly correlated with the tumor type, myometrial invasion and cervical involvement on histopathology (P < .05). Cases which had higher FIGO staging also had a higher detection rate on Pap smear (P < .05). CONCLUSION: The Pap smear may help in detection of endometrial carcinoma especially in cases with type 2 endometrial carinomas, tumor with cervical involvement and/or advanced FIGO stage.


Subject(s)
Cervix Uteri/pathology , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/pathology , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Female , Humans , Middle Aged , Papanicolaou Test/methods , Retrospective Studies , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathology , Vaginal Smears/methods
13.
Infect Control Hosp Epidemiol ; 42(2): 212-214, 2021 02.
Article in English | MEDLINE | ID: mdl-32746953

ABSTRACT

Healthcare workers (HCWs) have a theoretically increased risk of contracting severe acute respiratory coronavirus virus 2 (SARS-CoV-2) given their occupational exposure. We tested 2,167 HCWs in a London Acute Integrated Care Organisation for antibodies to SARS-CoV-2 in May and June 2020 to evaluate seroprevalence. We found a seropositivity rate of 31.6% among HCWs.


Subject(s)
COVID-19/epidemiology , COVID-19/immunology , Health Personnel/statistics & numerical data , Occupational Exposure/statistics & numerical data , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Viral/blood , COVID-19/diagnosis , COVID-19/virology , COVID-19 Serological Testing/methods , Humans , London/epidemiology , Middle Aged , Risk Factors , SARS-CoV-2/genetics , Seroepidemiologic Studies , State Medicine , Young Adult
14.
Mol Biol Rep ; 47(12): 9931-9937, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33159234

ABSTRACT

Among brain tumors, Medulloblastoma (MB) is one of the most common, malignant, pediatric tumors of the cerebellum. It accounts for ~20% of all childhood central nervous system (CNS) tumors. Despite, tremendous advances in drug development processes, as well as novel drugs for MB the morbidity and mortality rates, remain high. Craniospinal radiation, high-dose chemotherapy, and surgical resection are the primary therapeutic strategies. Tremendous progress in the field of "genomics" with vast amounts of data has led to the identification of four distinct molecular subgroups in medulloblastoma: WNT group, SHH group, group-III, and group-IV. The identification of these subgroups has led to individualized treatment strategies for each subgroup. Here, we discuss the various molecular subgroups of medulloblastoma as well as the differences between them. We also highlight the latest treatment strategies available for medulloblastoma.


Subject(s)
Cerebellar Neoplasms/classification , Medulloblastoma/classification , Humans
15.
Article in English | MEDLINE | ID: mdl-32897810

ABSTRACT

Advancement in the field of nanotechnology has increased the synthesis and exploitation of graphene-like nanomaterials. Graphene is a two-dimensional planar and hexagonal array of carbon atoms. Due to its flexible nature graphene and its derivatives have several significant prospects extending from electronics to life sciences and drug delivery systems. In this review, we enlist some of the toxic effects of graphene family nanomaterials (GFNs) in various aspects of biosystems viz., in vitro, in vivo, microbial, molecular and environmental. We also appreciate their extensive and promising applications though with some underlying challenges. This review also draws attention toward current and future prospect of global graphene market for wide-range commercialization.


Subject(s)
Environmental Pollutants/toxicity , Graphite/toxicity , Drug Delivery Systems , Nanostructures
16.
J Infect ; 81(3): 427-434, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32615198

ABSTRACT

BACKGROUND: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. METHODS: Cross-sectional 'snapshot' survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. FINDINGS: Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42-37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38-8.67; p = 0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. INTERPRETATION: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. FUNDING: Public Health England.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Disease Transmission, Infectious/statistics & numerical data , Health Personnel/statistics & numerical data , Pneumonia, Viral/epidemiology , Adult , Aged , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Cross-Sectional Studies , England , Female , Humans , Male , Medical Staff, Hospital/statistics & numerical data , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Prospective Studies , RNA, Viral , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
17.
J Cytol ; 37(4): 159-165, 2020.
Article in English | MEDLINE | ID: mdl-33776254

ABSTRACT

BACKGROUND: Metastasis to the breast of an extra-mammary origin is very rare. FNAC plays an important role in differentiating non-mammary breast metastasis from primary malignancy. This study aimed to analyze the cytomorphological criteria and its pitfalls in differentiating metastatic lesion of the breast from primary malignancy. METHODOLOGY: Retrospective analysis of 891 FNACs of the breast was performed for a time span of 3 years. A total of 12 cases were diagnosed on FNAC as secondary neoplasms to the breast. Clinical and radiological data, along with Pap and MGG stained smears of each case were examined and correlated with the histopathology of the primary tumor. Statistical analysis was carried out. All cases of primary breast malignancies were excluded from our study. RESULTS: In 10 out of 12 cases, primary malignancies were identified as Plasma cell myeloma (one case), B-acute lymphoblastic leukemia (two cases), acute myeloid leukemia (one case); chronic myeloid leukemia (one case), Burkitt's lymphoma of the ovary (one case), Diffuse large B-cell lymphoma (one case), esophageal squamous cell carcinoma (one case), spindle cell sarcoma (one case) and squamous cell carcinoma of the cervix (one case). The remaining two cases in our study were misdiagnosed on cytology as metastasis and turned out to be breast primaries on histopathology. CONCLUSION: Our case series highlights the importance of FNAC to differentiate secondary lesions from primary breast malignancy and thus helps to avoid unnecessary surgery to the patient. It emphasizes on the need to keep in mind the possibility of metastatic breast neoplasms in the presence of unusual cytological features on FNAC.

18.
Haematologica ; 105(3): 687-696, 2020 03.
Article in English | MEDLINE | ID: mdl-31123028

ABSTRACT

Leukemic stem cells are multipotent, self-renewing, highly proliferative cells that can withstand drug treatments. Although currently available treatments potentially destroy blast cells, they fail to eradicate leukemic progenitor cells completely. Aldehyde dehydrogenase and STAT3 are frequently up-regulated in pre-leukemic stem cells as well as in acute myeloid leukemia (AML) expressing the CD34+CD38- phenotype. The Isatin analog, KS99 has shown anticancer activity against multiple myeloma which may, in part, be mediated by inhibition of Bruton's tyrosine kinase activation. Here we demonstrate that KS99 selectively targets leukemic stem cells with high aldehyde dehydrogenase activity and inhibits phosphorylation of STAT3. KS99 targeted cells co-expressing CD34, CD38, CD123, TIM-3, or CD96 immunophenotypes in AML, alone or in combination with the standard therapeutic agent cytarabine. AML with myelodysplastic-related changes was more sensitive than de novo AML with or without NPM1 mutation. KS99 treatment reduced the clonogenicity of primary human AML cells as compared to normal cord blood mononuclear cells. Downregulation of phosphorylated Bruton's tyrosine kinase, STAT3, and aldehyde dehydrogenase was observed, suggesting interaction with KS99 as predicted through docking. KS99 with or without cytarabine showed in vivo preclinical efficacy in human and mouse AML animal models and prolonged survival. KS99 was well tolerated with overall negligible adverse effects. In conclusion, KS99 inhibits aldehyde dehydrogenase and STAT3 activities and causes cell death of leukemic stem cells, but not normal hematopoietic stem and progenitor cells.


Subject(s)
Isatin , Leukemia, Myeloid, Acute , Animals , Antigens, CD34 , Cytarabine , Interleukin-3 Receptor alpha Subunit , Leukemia, Myeloid, Acute/drug therapy , Mice , Neoplastic Stem Cells , Nucleophosmin
19.
Diagn Cytopathol ; 47(8): 776-782, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31091023

ABSTRACT

BACKGROUND: Malignant lymphomas (ML) are often complicated by serous effusions. The present study is an attempt to cytologically assess a large series of serous effusions associated with ML, identify the immunoreactivity of cells and to evaluate the role of various ancillary methods in confirming and subtyping these cases. METHODS: A cross-sectional study of 4612 serous effusions was undertaken at the Department of Cytology, Gujarat Cancer and Research Institute by retrieving data from the year 2015 to 2017. Total 169 cases of ML, clinically suspicious, were included. All cerebrospinal fluids, serous effusions involved by myeloid neoplasms, and cases of primary effusion lymphomas were excluded from our study. Pap stained smears of all these serous effusions were examined. Ancillary methods such as immunohistochemistry were used to further subtype the positive cases using the WHO classification of hematopoietic and lymphoid neoplasms (2016). RESULTS: Out of total 169 clinically suspicious cases, 109 cases were cytologically positive for ML which included 73 (66.9%) pleural effusions, 34 (31.1%) ascitic fluids, and 2 (1.8%) pericardial effusions. T-lymphoblastic lymphoma (36.9%) and Burkitt's lymphoma (38.2%) were the most common ML involving the pleural and ascitic fluids respectively. Non-Hodgkin's lymphoma (NHL) more frequently involved the serous cavities than Hodgkin's lymphoma. (P value <.0001). Among the NHL, T-cell lymphomas more commonly lead to serous effusions than B-cell lymphomas (P value <.0048). CONCLUSION: Cytological examination of serous effusions is an accurate, prompt, affordable technique having diagnostic and therapeutic implications. With the help of ancillary methods, we can identify the phenotype of cells, classify as well as confirm our diagnosis.


Subject(s)
Ascitic Fluid/pathology , Cytodiagnosis/methods , Lymphoma/diagnosis , Lymphoma/pathology , Pleural Effusion/pathology , Tertiary Care Centers , Adolescent , Burkitt Lymphoma/pathology , Cell Shape , Cell Size , Child , Female , Humans , Male , Young Adult
20.
J Cell Biochem ; 120(5): 7701-7710, 2019 May.
Article in English | MEDLINE | ID: mdl-30390320

ABSTRACT

Follicle-stimulating hormone-follicle-stimulating hormone receptor (FSH-FSHR) interaction is one of the most thoroughly studied signaling pathways primarily because of being implicated in sexual reproduction in mammals by way of maintaining gonadal function and sexual fertility. Despite material advances in understanding the role of point mutations, their mechanistic basis in FSH-FSHR signaling is still confined to mystically altered behavior of sTYS335 (sulfated tyrosine) yet lacking a substantial theory. To understand the structural basis of receptor modulation, we choose two behaviorally contradicting mutations, namely S128Y (activating) and D224Y (inactivating), found in FSH receptor responsible for ovarian hyperstimulation syndrome and ovarian dysgenesis, respectively. Using short-term molecular dynamics simulations, the atomic scale investigations reveal that the binding pattern of sTYS with FSH and movement of the thumb region of FSHR show distinct contrasting patterns in the two mutants, which supposedly could be a critical factor for differential FSHR behavior in activating and inactivating mutations.

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